Stag2-dependent chromatin remodeling enforces the erythroid-specific Gata1 cistrome

Abstract

Anemia is the most common presenting symptom of myelodysplastic syndromes (MDS), clonal myeloid malignancies characterized by ineffective hematopoiesis and myelodysplasia. STAG2 mutations in MDS are linked to severe anemia, erythroid dysplasia, and erythropoietin resistance, yet how STAG2 regulates erythropoiesis has been unclear. Sudunagunta and colleagues reveal that STAG2-dependent cohesion-mediated chromatin remodeling modulates the erythroid specificity of the GATA1 cistrome and its loss creates an accessibility-driven GATA1 retargeting that underlies dyserythropoiesis in MDS.